Breakthroughs that change patients’ lives Confidential 1

Monovalent XBB.1.5

BNT162b2 COVID-19 Vaccine

ACIP Presentation

September 12, 2023
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Presentation Outline

Kayvon Modjarrad, M.D., Ph.D.

Executive Director, Viral Vaccines

Vaccine Research and Development, Pfizer Inc.

Variant Epidemiology

COVID-19 Updated Vaccine 

Approval Pathway

Monovalent XBB.1.5 BNT162b2 

Vaccine Activity Against 

Contemporary Omicron Sublineages

Clinical Update
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XBB Sublineages Continue to Dominate the Epidemiologic 

Landscape, Despite the Emergence of New Lineages

Growing Dominance of EG.5.1

Source: 3D Spike Model - Pfizer

Mutation Prediction - jbloomlab.github.io/SARS2-RBD-escape-calc

Source: GISAID - gisaid.org, data accessed/analyzed in Pizer, September 08, 2023

BA.2.86 has high mutational density in Spike 

protein but accounts for <1% of cases 
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Pathway for COVID-19 Variant-Adapted Vaccine Updates 

COVID-19

Vaccine 

Development

Early-stage development 

“at risk” and 

surveillance to inform 

variant selection

Manufacture (pre-clinical 

and CMC data), Regulatory 

Submissions and Review

Distribute Vaccines

Strain Selection FDA Authorization/Approval 

ACIP Recommendation

• In accordance with FDA guidance for licensure, preclinical/CMC 

data package submission and review help ensure timely 

availability of seasonal variant-matched vaccine, similar to the 

model for annual influenza vaccine updates.
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Clinical and Preclinical Experience with Variant-modified Vaccines –

Supported Bivalent BA.4/5 Vaccine Authorization

Modified Vaccine Age Group Vaccine Regimen Clinical Data Preclinical Data

Beta

monovalent

Omicron BA.1

monovalent

Omicron BA.1

bivalent

Omicron BA.4/5

bivalent

Omicron XBB.1.5

monovalent

12 to 55 years

>55 years Single Dose Ongoing

18 to 55 years

18 to 55 years

18 to 55 years

>55 years

6 months to 11 years

12 to 55 years

>55 years

Original Vaccine Variant Vaccine
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Booster Vaccination Study Design

Female Balb/c mice (10 per group) were experienced with a primary series of monovalent BNT162b2 Original vaccine and a 3rd booster dose of 

bivalent BNT162b2 (Original+BA.4/5) vaccine. Mice then received a 4th booster dose of either a bivalent BNT162b2 (Original+BA.4/5) or a monovalent 

BNT162b2 (XBB.1.5) vaccine.

Data were generated by same pseudovirus neutralization assay and from sera of same mouse study presented at VRBPAC June 15, 2023 meeting 

(https://www.fda.gov/media/169541/download).

Data on file: Pfizer-BioNTech. September 2023.

Vaccination Blood sample

Day: 0 21 105 134 160

Monovalent 

Original

Monovalent 

Original

Bivalent 

Original+BA.4/5

Bivalent 

Original+BA.4/5

Monovalent 

XBB.1.5
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Monovalent XBB.1.5 BNT162b2 Booster Vaccine Effectively Neutralized 

Predominant and Emerging Variants

Data were generated by the same pseudovirus neutralization assay and from sera of same mouse study that generated data that were presented at VRBPAC June 15, 2023 Meeting (https://www.fda.gov/media/169541/download).

50% Neutralization Titers are Geometric Mean Titers of 10 mice per vaccine group. LOD, limit of detection; the lowest serum dilution of 1:20. 

Original + BA.4/5 XBB.1.5

10

1

10

2

10

3

10

4

10

5

422

1249

572

4069

440

2043

50% Neutralization Titer LOD

Vaccine Group

XBB.1.5 EG.5.1 BA.2.86
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Monovalent XBB.1.5 BNT162b2 Booster Vaccine Elicited Substantially Higher 

Neutralizing Response Compared to the Bivalent Vaccine

Data were generated by same pseudovirus neutralization assay and from sera of same mouse study that generated data that were presented at VRBPAC June 15, 2023 Meeting (https://www.fda.gov/media/169541/download).

GMR = Geometric Mean Ratio of the Geometric Mean Titer (GMT) of Monovalent XBB.1.5 divided by GMT of WT+BA.4/5 group. LOD, limit of detection; the lowest serum dilution of 1:20. 

Original + BA.4/5 XBB.1.5

0.1

1

10

100

GMR (relative to Original + BA.4/5)

Vaccine Group

XBB.1.5 EG.5.1 BA.2.86

5

7

3
STRICTLY CONFIDENTIAL CC-9

Vaccination Blood sample

Day: 0 21 49

Bivalent 

(Original/BA.4/5)

Monovalent 

XBB.1.5

Bivalent 

(Original/BA.4/5)

Monovalent 

XBB.1.5

Primary Series Study Design

Female Balb/c mice (10 per group) were administered 2 doses (21 days apart) of either bivalent BNT162b2 (Original+BA.4/5) or monovalent 

BNT162b2 (XBB.1.5) vaccine.

Data were generated by same pseudovirus neutralization assay and from sera of same mouse study presented at VRBPAC June 15, 2023 meeting 

(https://www.fda.gov/media/169541/download).

Data on file: Pfizer-BioNTech. September 2023.
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These data were generated by same pseudovirus neutralization assay and from sera of same mouse study that generated data that were presented at VRBPAC June 15, 2023 Meeting (https://www.fda.gov/media/169541/download).

50% Neutralization Titers are Geometric Mean Titers of 10 mice per vaccine group. 

LOD, limit of detection; the lowest serum dilution of 1:20. 

Monovalent XBB.1.5 BNT162b2 Primary Series Effectively Neutralized 

EG.5.1 and XBB.1.5

Original + BA.4/5 XBB.1.5

10

1

10

2

10

3

10

4

10

5

84

5396

111

3653

50% Neutralization Titer LOD

Vaccine Group

XBB.1.5 EG.5.1
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Monovalent XBB.1.5 BNT162b2 Primary Series Elicited Substantially Higher 

Neutralizing Response Compared to the Bivalent Vaccine

These data were generated by same pseudovirus neutralization assay and from sera of same mouse study that generated data that were presented at VRBPAC June 15, 2023 Meeting (https://www.fda.gov/media/169541/download).

GMR = Geometric Mean Ratio of the Geometric Mean Titer (GMT) of Monovalent XBB.1.5 and Bivalent XBB.1.5+BA.4/5 divided by GMT of WT+BA.4/5 group. 

LOD, limit of detection; the lowest serum dilution of 1:20. 

Original + BA.4/5 XBB.1.5

0.01

0.1

1

10

100

GMR (relative to Original + BA.4/5)

Vaccine Group

XBB.1.5 EG.5.1

33

64
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Monovalent XBB.1.5 BNT162b2 Clinical Study in 

Individuals ≥ 12 years

Monovalent XBB.1.5 BNT162b2 30μg

Group 1 (n=200): 12- 55 years

Group 2 (n=200): >55 years
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• The SARS-CoV-2 epidemiologic landscape remains dominated by XBB 

sublineages.

• Monovalent XBB.1.5 BNT162b2 is equally immunogenic against XBB.1.5, 

EG.5.1 and BA.2.86, in a COVID-19 vaccine-experienced preclinical study.

• Variant-adapted vaccines improve immune responses against antigenically 

matched and closely related strains.

• A preclinical/CMC package for variant-adapted COVID-19 vaccine fulfilled 

licensure criteria.

Summary
Breakthroughs that change patients’ lives Confidential 14

Monovalent XBB.1.5

Pfizer-BioNTech COVID-19 

Vaccine

ACIP

September 12, 2023